scholarly journals Inhaled corticosteroids use in childhood respiratory diseases: an italian survey on pediatricians’ prescription habits

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Giovanni Cerimoniale ◽  
Paolo Becherucci ◽  
Maria Carmen Verga ◽  
Giuseppe Di Mauro ◽  
Luciana Indinnimeo ◽  
...  
Keyword(s):  
Primary Care ◽  
Respiratory Diseases ◽  
Low Dose ◽  
Inhaled Corticosteroids ◽  
Persistent Asthma ◽  
High Dose ◽  
Dose Therapy ◽  
Asthma Exacerbations ◽  
Long Term Treatment ◽  
Primary Care Pediatricians

Abstract Background A national consensus document on inhaled corticosteroids (ICS) use in childhood, produced by the main Italian pediatric scientific societies, has been recently released. The aim of this study was to gather information on the current pediatricians’ ICS prescription habits in Italy for the management of the most common pediatric respiratory diseases, namely allergic rhinitis (AR), asthma, preschool wheezing and laryngitis. Methods From the 1st October 2018 to the 31st January 2019 a link to an online questionnaire was sent monthly through a newsletter to the members of the Italian Society of Pediatrics. The questionnaire included 18 items on ICS use in the most common pediatric respiratory diseases. Data collection and reporting was based on STROBE Statement Checklist for cross-sectional studies. Results One thousand-two questionnaires were returned from primary care pediatricians (39.1%), hospital pediatricians (38.7%), private practicers (16.4%), university pediatricians (3.1%) and Pediatrics residents (2.7%). We found a good adherence to the international guidelines on AR, with prevalent use of oral antihistamine (60.6%) in the secretive phenotype and nasal ICS in the obstructive phenotype (64.8%). In asthma exacerbations ICS are not used in 53.4% of cases, but they are used at high dose in 27.9% and at low dose in 18.7% of cases. In intermittent asthma, ICS are not chosen as a daily controller therapy in 54.1% of cases, while they are chosen as a low dose daily therapy in 44.5% of cases (high dose in 1.4%). In children with persistent asthma, ICS are chosen as a daily low dose therapy in 67.4% of cases and as a daily high dose therapy in 31%. In the management of preschool wheezing, when a long-term treatment is needed, ICS are chosen both alone and in association with antileukotrienes in 71.4% of cases. Children affected by recurrent asthma exacerbations and wheezing are closely followed up, in particular by their primary care pediatricians. The preference for certain molecules in the treatment of different respiratory diseases also emerged. Conclusions Pediatricians’ ICS prescription habits in Italy should be improved, especially in the management of asthma. Future surveys on a more numerous sample will be useful to analyze differences in prescription habits on the basis of pediatricians’ work settings and geographical distribution.

Wirksamkeit und Sicherheit von Dupilumab bei ganzjähriger allergischer Rhinitis und gleichzeitigem Asthma

2019 ◽  
Vol 7 (1) ◽  
pp. 27-28
Author(s):  
Susanne Lau
Keyword(s):  
Allergic Rhinitis ◽  
Inhaled Corticosteroids ◽  
Persistent Asthma ◽  
High Dose ◽  
Specific Response ◽  
Pivotal Phase ◽  
Runny Nose ◽  
Asthma Patients ◽  
Long Acting ◽  
Snot 22

Background: Dupilumab, an anti-IL-4 receptor a mAb, inhibits IL-4/IL-13 signaling, key drivers of type 2/TH2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting b2-agonists. Objective: To examine dupilumabʼs effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR). Methods: A post hoc analysis reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w) doses under investigation in phase 3 (NCT02414854) was carried out. PAR was defined at study entry as a specific response to typical perennial antigens (IgE >0.35 Ku/L). Results: Overall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT-22 total score (least squares mean difference, 25.98; 95% CI, 210.45 to 21.51; P 5.009) and all 4 AR-associated symptoms evaluated (nasal blockage, 20.60; 95% CI, 20.96 to 20.25; runny nose, 20.67; 95% CI, 21.04 to 20.31; sneezing, 20.55; 95% CI, 20.89 to 20.21; postnasal discharge, 20.49; 95% CI, 20.83 to 20.16; all P < .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant, decreases in SNOT-22 total score (21.82; 95% CI, 26.46 to 2.83; P 5 .443 vs placebo) and in each ARassociated symptom. In patients without PAR, no differences were observed for these measures versus placebo. Conclusions: Dupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.

INDUCTION OF OSTEOPOROSIS IN RATS BY STANDARD HEPARIN AND LOW MOLECULAR WEIGHT HEPARIN

1987 ◽  
Author(s):  
T Mätzsch ◽  
D Berggvist ◽  
U Hedner ◽  
B Nilsson ◽  
P Østergaard
Keyword(s):  
Molecular Weight ◽  
Bone Mass ◽  
Low Molecular Weight Heparin ◽  
Low Dose ◽  
Term Treatment ◽  
Ash Content ◽  
Low Molecular Weight ◽  
High Dose ◽  
Degree Of Reduction ◽  
Long Term Treatment

Long-term treatment with heparin can induce osteoporosis. This complication is suspected to be related to the dosage of heparin rather than to duration of therapy, but the mechanism by which heparin induces osteoporosis is unknown. In a previous study we reported the same degree of reduction in mineral bone mass in rats after treatment with 2 IU heparm/g bw for 33 and 65 days (Thromb Haemostas 1986,56:293-4). Using the same animal model we compared the effect of a high-dose standard heparin (SH) and a low molecular weight heparin (LMWH) in a high and a low dose on the mineral bone mass in the femur of rats. Method: 60 female Wistar rats (207±1.8 g) were randomly allocated to treatment with either 2 Xal U/g bw of standard heparin (SH), 2 Xal U/g bw of LMWH ("high-dose"), 0.4 Xal U/g bw LMWH ("low-do-se") or placebo (saline). A standard sodium salt heparin of porcine origin was used, and the LMWH was an enzymatically depolymerized pork mucosal heparin (LHN-1, mean MW 4900 D). Treatment with s.c. injections was continued for 34 days. 24 hours after the last injection the rats were sacrificed and the carefully cleaned femora weighed in air and in water under standardized conditions. Volumes and densities were calculated from the weights. The bones were then incinerated for 48 hours at 600°C and weighed again to determine the ash content (expressed as ash weight per ml of unashed femur volume). Results: There was a significant decrease in ash content (p<0.01) and density (p<0.01) of the femora in all heparin treated groups as compared with controls. High-dose LMWH caused the same reduction in bone mineral mass as standard heparin. Treatment with low-dose LMWH resulted in a significantly less pronounced reduction in ash content (p<0.001) and density (p<0.05) of the femora when compared with high-dose standard heparin and high-dose LMWH. CONCLUSION: Daily injections of 2 Xal U/g body weight of standard heparin or low molecular weight heparin for 34 days causes the same degree of reduction of mineral bone mass in rats. The reduction of mineral bone mass in rats by treatment with low molecular weight heparin is dose dependent.

scholarly journals Efficacy of NS-718, a Novel Lipid Nanosphere-Encapsulated Amphotericin B, againstCryptococcus neoformans

1998 ◽  
Vol 42 (7) ◽  
pp. 1722-1725 ◽  
Author(s):  
Mohammad Ashraf Hossain ◽  
Shigefumi Maesaki ◽  
Hiroshi Kakeya ◽  
Tetsuhiro Noda ◽  
Katsunori Yanagihara ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Agent ◽  
Low Dose ◽  
Yeast Cells ◽  
High Dose ◽  
Pulmonary Cryptococcosis ◽  
High Dose Therapy ◽  
Dose Therapy

ABSTRACT In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC forCryptococcus neoformans. In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.

Low-dose versus high-dose therapy for Gaucher disease: goals and markers

Blood ◽  
2007 ◽  
Vol 109 (1) ◽  
pp. 387-387 ◽  
Author(s):  
Carla E. M. Hollak ◽  
Maaike de Fost ◽  
Johannes M. F. G. Aerts ◽  
Stephan vom Dahl
Keyword(s):  
Gaucher Disease ◽  
Low Dose ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy

Cyproterone acetate as initial treatment and maintenance therapy for hirsutism

1985 ◽  
Vol 109 (4) ◽  
pp. 522-529 ◽  
Author(s):  
I. M. Holdaway ◽  
M. S. Croxson ◽  
H. K. Ibbertson ◽  
A. Sheehan ◽  
B. Knox ◽  
...  
Keyword(s):  
Growth Rate ◽  
Side Effects ◽  
Maintenance Therapy ◽  
Cyproterone Acetate ◽  
Hair Growth ◽  
Low Dose ◽  
Sex Hormone Binding Globulin ◽  
Plasma Testosterone ◽  
High Dose ◽  
Dose Therapy

Abstract. Thirty-four patients with hirsutism were treated for 9 months with 100 mg cyproterone acetate (CA) given on days 5–15 of the menstrual cycle together with a combination oral contraceptive containing 2 mg CA and 50 μg ethinyloestradiol (Diane®) given on days 5–25 of the cycle. After 9 months treatment patients were randomised to a 12 month double-blind cross-over trial comparing Diane® plus 25 mg CA with Diane® plus placebo, to test the efficacy of low-dose CA as maintenance therapy. Thirty-one patients (92%) experienced moderate or good subjective improvement in hirsutism on high-dose CA, associated with a 40% mean overall improvement in objective hirsutism grade and 13% overall reduction in hair growth rate measured by a photographic technique. Minor or moderate side effects were experienced by 64% of patients and severe side effects by 11% at this dosage. There was a mean subjective relapse rate of 33% when patients were changed to low dose CA, and relapse rates were not significantly different between the two regimens with 28% relapsing on 25 mg CA + Diane® and 48% on placebo and Diane® (P < 0.05). Despite significant subjective relapse with low-dose treatment there was no significant deterioration in objective hirsutism grade or hair growth rate determined photographically. Levels of plasma testosterone, sex hormone binding globulin, free testosterone (derived) and androstenedione fell significantly on high dose CA and this reduction was maintained during low dose therapy. Cyproterone acetate at high dosage thus appeared an effective agent in the treatment of hirsutism, but 33% of patients considered they deteriorated when changed to low-dose therapy despite maintenance of androgen suppression and lack of change in objective measurements. Maintenance therapy after remission with high-dose CA appears justified since 60% of patients underwent subjective relapse when all treatment was stopped.

Comparison of Blood Graft Cellular Content in Myeloma (MM) Patients and Non-Hodgkin Lymphoma (NHL) Patients Mobilized with Chemotherapy Plus G-CSF with or without Plerixafor

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4414-4414
Author(s):  
Esa Jantunen ◽  
Ville Varmavuo ◽  
Raija Silvennoinen ◽  
Piia Valonen ◽  
Taru Kuittinen ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Low Dose ◽  
Lymphoid Cells ◽  
High Dose ◽  
Cellular Composition ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Non Hodgkin Lymphoma ◽  
Previous Therapy ◽  
Cd34 Cells

Abstract Abstract 4414 Background: Cellular composition of blood graft collected to support high-dose therapy may have important implications in regard to hematopoietic and immune reconstitution after high-dose therapy. Mobilization method used may have effect on graft composition as well as previous therapy given to the patients. Methods: We have retrospective analyzed by flow cytometry cellular composition of freezed blood grafts in 34 patients with NHL (chemotherapy + G-CSF mobilization 15, add-on plerixafor 19 patients) and compared the observations with those of 17 MM patients mobilized either with low-dose cyclophosphamide + G-CSF (n=12) or with add-on plerixafor (n=5). The analyses were performed from the first graft collected from the chemomobilized patients or from the first draft collected after the plerixafor injection, respectively. Antibodies used included CD34, CD38, CD133 in regard to CD34+ subclasses and CD3, CD4, CD8, CD19 and CD3CD16/CD56 to analyze lymphocyte subsets. In addition, 7-aminoactinomycin D staining was used to assess the amount of nonviable CD34+ and lymphoid cells. Results: In regard to the patients mobilized without plerixafor, MM patients had higher content of CD34+ cells (4.9 vs. 2.0 × 106/kg, p=0.009) as well as lower proportion of more primitive stem cells (0.8 vs. 1.9 % of all CD34+ cells, p=0.075) when compared to NHL patients. The amount of B-lymphocytes was also significantly higher in MM patients (0.5 × 106/kg vs. 0.0, p< 0.001). No differences were observed in the total amount of T (CD3+) cells, NK cells or in the proportion of nonviable CD34+ or lymphoid cells. Of the plerixafor treated patients, the amount of B-lymphocytes was higher in MM patients (1.8 × 106/kg vs. 0.0, p<0.001) as well as CD4/CD8 ratio (2.56 vs. 1.0, p=0.004) when compared to NHL patients. Conclusion: As there appears to be differences between MM and NHL patients mobilized with or without plerixafor, it might be advisable to analyze separately effects of mobilization therapy to graft content and post-transplant outcomes in these diseases. Apparently the type and intensity of previous therapy given to the patients (e.g. rituximab) has important effects on graft cellular composition. Disclosures: Jantunen: Genzyme: Has participated in EU Leadership meeting organized by Genzyme as well as Medical Advisory Board meeting organized by Genzyme Other, Honoraria. Silvennoinen:Genzyme: Consultancy.

Long Term Efficacy and Safety Results and Analysis of Dose Correlations from the Phase I/II Peginvera Study of Ropeginterferon Alfa-2b, a Novel IFNa-2b, in Polycythemia Vera Patient

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4056-4056
Author(s):  
Heinz Gisslinger ◽  
Veronika Buxhofer-Ausch ◽  
Josef Thaler ◽  
Ernst Schlögl ◽  
Gunther Gastl ◽  
...  
Keyword(s):  
Research Funding ◽  
Dose Group ◽  
Low Dose ◽  
Term Treatment ◽  
High Dose ◽  
Individual Response ◽  
Molecular Response ◽  
Efficacy And Safety ◽  
Long Term Treatment

Abstract Background Ropeginterferon alfa-2b (AOP2014/P1101) is a novel long-acting pegylated IFN-alpha-2b, composed of mainly one isoform, resulting in longer half-life and exposure time. Reduced dosing frequencies, better tolerability, improved compliance and more favorable long-term treatment outcomes in patients with polycythemia vera (PV) are expected. The drug has Orphan designation by EMA and FDA and is currently in the phase III stage of development. Study design Efficacy and safety data are being collected in the follow-up extension stage of the study (collecting the data of both Phase I and Phase II portions of the study), after the maximum tolerated dose (MTD) of ropeginterferon alfa-2b, administered subcutaneously every 14 to 28 days, has been defined earlier. Patients with confirmed diagnosis of PV, age ≥18 years, both naïve and cytoreductively pre-treated were eligible. After establishing the MTD, an extended cohort of 25 additional patients has been planned to be recruited. Complete hematological response (CR) is defined by hematocrit (Hct)<45%, platelet count≤400*109/L, WBC count≤10*109/L, normal spleen size by sonography, and absence of thromboembolic events. Partial response (PR) is defined as Hct<45% without phlebotomy but with persistent splenomegaly or elevated (>400*109/L) platelet count, or reduction of phlebotomy requirements by at least 50%. Complete molecular response has been defined as reduction of any molecular abnormality to undetectable levels; partial molecular response as: reduction ≥ 50% in patients with < 50% mutant allele burden, or a reduction ≥ 25% in patients with > 50% mutant allele burden. The present analysis was focused on long-term tolerability and safety in correlation with the dose of ropeginterferon alfa-2b in PV. Results Data on treatment as by July, 24, 2015, are covered by the current analysis. Baseline characteristics of the study cohort during short-term treatment were already presented earlier (Gisslinger et al, ASH 2013). The full analysis set and efficacy set were composed of 51 and 47 patients, respectively. Currently, the median reported treatment duration is 138 weeks, 33 patients completed their follow up for two years, 19 for three years. Starting with the week 10, Hct-level, platelet- and WBC-counts could be constantly maintained within normal range in the majority of patients. In a group of patients with the mean administered dose of <300 µg ("low dose", n=36), CR as best individual response was achieved in 20 (56%) patients, and PR in 14 (39%) compared to the CR and PR in the high dose (>300 µg, n=11) group of 8 (73%) and 3 (27%) respectively. However, no statistical significance can be observed if correlation between the dose and response status was analyzed. 30 patients are still being treated in the study. Similarly, no association between the dose and occurrence of adverse events in the study could be observed. Complete molecular response as best individual response was observed more frequently in the high dose group 4 (36%) compared to 8 (23%) in the low dose group, while partial molecular responses were equally frequent in both dose groups (in 6/55% and 20/57%, respectively). 21 patients discontinued the study, 18 being treated with AOP2014 doses corresponding to low, and 3 to the high dose arms, corresponding to the drop-out rate of 50% and 27% in the respective arms. Interestingly, all discontinuations in the high dose group occurred within the first year of treatment (at weeks 16, 18 and 32), while the drop-outs in the low dose group (6 patients, 33%) discontinued the study after completion of their first year of treatment. Conclusions Efficacy and safety profile remain in line with expectations from other (pegylated) interferons. Overall response rate of >80% with cumulative CRs in 45-50%, accompanied by phlebotomy independence, normalization of hematological parameters and spleen size reduction in majority of patients have been observed. Significant and sustained JAK2 allelic burden decrease, starting from week 28 of treatment, was seen. No significant difference between the two mean dose levels regarding response rates or adverse events even during long-term treatment and observation could be observed. These finding are to be further verified in a larger prospective setting. Disclosures Gisslinger: Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; AOP ORPHAN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Geron: Consultancy; Sanofi Aventis: Consultancy; Janssen Cilag: Honoraria, Speakers Bureau. Buxhofer-Ausch:AOP Orphan: Research Funding. Thaler:AOP Orphan: Research Funding. Schlögl:AOP Orphan: Research Funding. Gastl:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; AOP Orphan: Research Funding. Ban:AOP Orphan: Research Funding. Egle:AOP Orphan: Research Funding. Melchardt:AOP Orphan: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria, Research Funding; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Willenbacher:COMET Center ONCOTYROL: Research Funding; AOP Orphan: Research Funding. Kralovics:AOP Orphan: Research Funding; Qiagen: Membership on an entity's Board of Directors or advisory committees. Zörer:AOP Orphan: Employment. Ammann-Mwathi:AOP Orphan: Employment. Kadlecova:AOP Orphan: Consultancy. Zagrijtschuk:AOP Orphan: Employment. Klade:AOP Orphan: Employment. Greil:Pfizer: Honoraria, Research Funding; GSK: Research Funding; Boehringer-Ingelheim: Honoraria; AOP Orphan: Research Funding; Celgene: Consultancy; Janssen-Cilag: Honoraria; Genentech: Honoraria, Research Funding; Novartis: Honoraria; Astra-Zeneca: Honoraria; Amgen: Honoraria, Research Funding; Ratiopharm: Research Funding; Sanofi Aventis: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; Roche, Celgene: Honoraria, Research Funding.

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